9-134433976-T-G

Variant names:

• chr9-134433976-T-G
• rs3132293
• NM_002957.6:c.1136-126T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002957.6(RXRA):​c.1136-126T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 10 publications found

Genes affected

RXRA (HGNC:10477): (retinoid X receptor alpha) Retinoid X receptors (RXRs) and retinoic acid receptors (RARs) are nuclear receptors that mediate the biological effects of retinoids by their involvement in retinoic acid-mediated gene activation. These receptors function as transcription factors by binding as homodimers or heterodimers to specific sequences in the promoters of target genes. The protein encoded by this gene is a member of the steroid and thyroid hormone receptor superfamily of transcriptional regulators. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2014]

RXRA Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002957.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXRA	NM_002957.6	MANE Select	c.1136-126T>G		intron	N/A	NP_002948.1	P19793-1
	RXRA	NM_001291920.2		c.1055-126T>G		intron	N/A	NP_001278849.1	A0A5F9ZHH6
	RXRA	NM_001291921.2		c.845-126T>G		intron	N/A	NP_001278850.1	P19793-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXRA	ENST00000481739.2	TSL:1 MANE Select	c.1136-126T>G		intron	N/A	ENSP00000419692.1	P19793-1
	RXRA	ENST00000672570.1		c.1055-126T>G		intron	N/A	ENSP00000500402.1	A0A5F9ZHH6
	RXRA	ENST00000356384.4	TSL:5	n.1546-126T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151862 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 501416 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 262586

African (AFR) AF: 0.00 AC: 0 AN: 13620

American (AMR) AF: 0.00 AC: 0 AN: 21584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14158

East Asian (EAS) AF: 0.00 AC: 0 AN: 30964

South Asian (SAS) AF: 0.00 AC: 0 AN: 48728

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30786

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2300

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 311734

Other (OTH) AF: 0.00 AC: 0 AN: 27542

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151862 Hom.: 0 Cov.: 31 AF XY: 0.0000270 AC XY: 2 AN XY: 74158

African (AFR) AF: 0.00 AC: 0 AN: 41384

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5120

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67916

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 6173

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.49
DANN	Benign	0.23
PhyloP100		-1.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3132293; hg19: chr9-137325822;